This program project explores the effects of fatty acids, lipid oxidation products, eicosanoids, and lipoproteins in vascular biology and atherosclerosis. There are four research projects. Project 1 deals with the effects of polyunsaturated fatty acids (PUFA) and oxidized PUFA products on the properties and function of cultured arterial endothelial and smooth muscle cells. It will investigate the role of peroxisomal oxidation in PUFA metabolism the incorporation of PUFA oxidation products into arterial cells, and the effects of these oxidation products on leukocyte adhesion molecule expression in endothelial cells and the function of ion channels in vascular smooth muscle cells. Project 2 utilizes the CaCo-2 cell model to study intestinal lipoprotein production. It will investigate the incorporation of PUFA and cholesterol oxidation products into intestinal lipoproteins, and the effect of these oxidized lipids on the assembly and secretion of intestinal lipoproteins. Project 3 involves receptor-mediated clearance of triglyceride-rich lipoproteins. The role of lipoprotein lipase and hepatic triglyceride lipase on the clearance of these lipoproteins by members of the low density lipoprotein class of lipoprotein receptors will be investigated using cell culture and transgenic animal approaches. Project 4 focuses on the effects of two arachidonic acid mediators formed by the cytochrome P450 pathway, epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) on the regulation of coronary blood flow in isolated coronary rings and miscrovessel preparations. The projects are supported by two core units, Cell Culture and Administration. Through collaboration of experts in lipid biochemistry, cell culture, lipoprotein production, lipoprotein receptors, eicosanoids, vasoreactivity, adhesion molecules, patch clamping, microvascular physiology, and gene vector constructs, our group can bring many powerful approaches to the solution of important questions in vascular biology. Our overall goal is to provide new basic insight into the role of lipids and lipoproteins in the functional responses of the arterial wall and the mechanisms of atherogenesis.